| 1. |
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| 2. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Godambe, S. V., et al.
(författare)
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Very high energy γ-ray and near infrared observations of 1ES2344+514 during 2004 05
- 2007
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 34, s. 1683-1695
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Tidskriftsartikel (refereegranskat)abstract
- We have observed the BL Lac object 1ES2344+514 (z = 0.044) in very high energy (VHE) gamma-ray and near-infrared wavelength bands with TACTIC and MIRO telescopes, respectively. The observations were made from 18th October to 9th December 2004 and 27th October 2005 to 1st January 2006. Detailed analysis of the TACTIC data indicates the absence of a statistically significant gamma-ray signal both in overall data and on a nightly basis from the source direction. We estimate an upper limit of I(≥1.5 TeV) ≤ 3.84 × 10−12 photons cm−2 s−1 at a 3σ confidence level on the integrated γ-ray flux. In addition, we have also compared TACTIC TeV light curves with those of the RXTE ASM (2–12 keV) for the contemporary period and find that there are no statistically significant increases in the signal strengths from the source in both these energy regions. During 2004 IR observations, 1ES2344+514 shows low level (0.06 magnitude) day-to-day variation in both, J and H bands. However, during the 2005 observation epoch, the source brightens up by about 0.41 magnitude from its October 2005 level J magnitude = 12.64 to J = 12.23 on December 6, 2005. It then fades by about 0.2 magnitude during 6 to 10 December, 2005. The variation is seen in both, J and H, bands simultaneously. The light travel time arguments suggest that the emission region size is of the order of 1017 cm.
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| 5. |
- Koul, R., et al.
(författare)
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The TACTIC atmospheric Cherenkov imaging telescope
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 578:3, s. 548-564
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Tidskriftsartikel (refereegranskat)abstract
- The TACTIC (TeV Atomospheric Cherenkov Telescope with Imaging Camera) γγ-ray telescope, equipped with a light collector of area ∼9.5m2 and a medium resolution imaging camera of 349 pixels, has been in operation at Mt. Abu, India, since 2001. This paper describes the main features of its various subsystems and its overall performance with regard to (a) tracking accuracy of its two-axes drive system, (b) spot size of the light collector, (c) back-end signal processing electronics and topological trigger generation scheme, (d) data acquisition and control system and (e) relative and absolute gain calibration methodology. Using a trigger field-of-view of 11×1111×11 pixels (∼3.4∘×3.4∘)(∼3.4∘×3.4∘), the telescope records a cosmic ray event rate of ∼2.5Hz at a typical zenith angle of 15∘15∘. Monte Carlo simulation results are also presented in the paper for comparing the expected performance of the telescope with actual observational results. The consistent detection of a steady signal from the Crab Nebula above ∼1.2TeV energy, at a sensitivity level of ∼5.0σ∼5.0σ in ∼25h, alongwith excellent matching of its energy spectrum with that obtained by other groups, reassures that the performance of the TACTIC telescope is quite stable and reliable. Furthermore, encouraged by the detection of strong γγ-ray signals from Mrk 501 (during 1997 and 2006 observations) and Mrk 421 (during 2001 and 2005–2006 observations), we believe that there is considerable scope for the TACTIC telescope to monitor similar TeV γγ-ray emission activity from other active galactic nuclei on a long-term basis.
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| 6. |
- Godambe, S. V., et al.
(författare)
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Very high energy γ-ray observations of Mrk 501 using the TACTIC imaging γ-ray telescope during 2005 06
- 2008
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:6
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report on the Markarian 501 results obtained during our TeV γ-ray observations from 11 March to 12 May 2005 and 28 February to 7 May 2006 for 112.5 h with the TACTIC γ-ray telescope. During 2005 observations for 45.7 h, the source was found to be in a low state and we have placed an upper limit of 4.62 × 10−12 photons cm−2 s−1 at 3σ level on the integrated TeV γ-ray flux above 1 TeV from the source direction. However, during 2006 observations for 66.8 h, detailed data analysis revealed the presence of a TeV γ-ray signal from the source with a statistical significance of 7.5σ above Eγ≥ 1 TeV. The time-averaged differential energy spectrum of the source in the energy range 1–11 TeV is found to match well with the power-law function of the form (dΦ/dE = f0E−Γ) with f0 = (1.66 ± 0.52) × 10−11 cm−2 s−1 TeV−1 and Γ = 2.80 ± 0.27.
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| 7. |
- Yadav, K. K., et al.
(författare)
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Observations of TeV γ-rays from Mrk 421 during December 2005 to April 2006 with the TACTIC telescope
- 2007
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 27:5, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- The TACTIC γ-ray telescope has observed Mrk 421 on 66 clear nights from December 07, 2005 to April 30, 2006, totalling ∼202 h of on-source observations. Here, we report the detection of flaring activity from the source at ⩾1 TeV energy and the time-averaged differential γ-ray spectrum in the energy range 1–11 TeV for the data taken between December 27, 2005 and February 07, 2006 when the source was in a relatively higher state as compared to the rest of the observation period. Analysis of this data spell, comprising ∼97 h reveals the presence of a ∼12.0σ γ-ray signal with daily flux of >1 Crab unit on several days. A pure power law spectrum with exponent −3.11 ± 0.11 as well as a power law spectrum with an exponential cutoff (Γ = −2.51 ± 0.26 and E0 = (4.7 ± 2.1) TeV) are found to provide reasonable fits to the inferred differential spectrum within statistical uncertainties. We believe that the TeV light curve presented here, for nearly 5 months of extensive coverage, as well as the spectral information at γ-ray energies of >5 TeV provide a useful input for other groups working in the field of γ-ray astronomy.
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| 8. |
- Dhar, V. K., et al.
(författare)
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ANN based energy estimation procedure and energy spectrum of the Crab Nebula as measured by the TACTIC gamma-ray telescope
- 2005
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Ingår i: 29th International Cosmic Ray Conference Pune (2005). ; , s. 179-182
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Konferensbidrag (refereegranskat)abstract
- A novel energy reconstruction procedure based on the utilization of Articial Neural Network has been developedfor the TACTIC atmospheric Cerenkov imaging telescope to estimate the energy of the primary gammaraysin the TeV energy range. The procedure uses a 3:20:1 conguration of the ANN with resilient backpropagationtraining algorithm to estimate the energy of a-ray like event on the basis of its image SIZE,DISTANCE and zenith angle. The results obtained by using the CORSIKA code simulated data suggest theenergy resolution of the telescope is40for retaining90of the-ray events in a particular energybin which is comparable to the energy resolution of other single element imaging telescopes. Details of theenergy estimation procedure along with results obtained by determining the Crab Nebula energy spectrum inthe energy range 1-16 TeV as measured by the TACTIC telescope are presented in the paper.
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| 9. |
- Godambe, S. V., et al.
(författare)
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Very High Energy Gamma-ray and Near Infrared observations of 1ES2344+514 with TACTIC and MIRO Telescopes
- 2005
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Ingår i: 29th International Cosmic Ray Conference Pune (2005).
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Konferensbidrag (refereegranskat)abstract
- 1ES2344+514 (z = 0.04) is one of the rst BL Lac objects to be reported as an extreme synchrotron blazar withsynchotron peak energy reaching up to 100keV and was discovered as a source of Very High Energy (VHE)gamma- rays by the Whipple group in 1995. Subsequently, it was observed by the HEGRA group in 1997/98and 2002. We have recently (Oct.- Dec. 2004) observed the 1ES2344+514 using the imaging element of theTACTIC array and have collected data for 53 hours in on/off mode. The source was also observed in nearinfrared bands J, H and K, for some nights using NICMOS-3 array mounted on 1.2m MIRO infrared telescope.Such a study is expected to provide clues to the dominance or otherwise of the Compton component. Afterdetailed analysis of the TACTIC data we have placed an upper limit of photons cmsata 3condence level on the gamma-ray ux from the source. In the near infrared band the source shows lowlevel variations without any aring activity.
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| 10. |
- Tickoo, A. K., et al.
(författare)
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A generalized ray-tracing procedure for an atmospheric Cherenkov imaging telescope and optical characteristics of the TACTIC light collector
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 539:1-2, s. 177-190
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Tidskriftsartikel (refereegranskat)abstract
- A generalized ray-tracing procedure has been developed, which facilitates the design of a multimirror-based light collector used in atmospheric Cherenkov telescopes. This procedure has been employed to study the optical characteristics of the 3.5 m diameter light collector of the TACTIC Imaging telescope. Comparison of the measured point-spread function of the light collector with the simulated performance of ideal Davies–Cotton and paraboloid designs has been made to determine an optimum arrangement of the 34 spherical mirror facets used in the telescope to obtain the best possible point-spread function. A description of the ray-tracing subroutine used for processing CORSIKA-generated Cherenkov data, required for carrying out Monte-Carlo simulation studies, is also discussed in the paper.
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| 11. |
- Yadav, K. K., et al.
(författare)
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Search for TeV γ-rays from H1426+428 during 2004-2007 with the TACTIC telescope
- 2009
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 36:8
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Tidskriftsartikel (refereegranskat)abstract
- The BL Lac object H1426+428 (z ≡ 0.129) is an established source of TeV γ-rays and detections of these photons from this object also have important implications for estimating the extragalactic background light in addition to the understanding of the particle acceleration and γ-ray production mechanisms in the AGN jets. We have observed this source for about 244 h in 2004, 2006 and 2007 with the TACTIC γ-ray telescope located at Mt Abu, India. Detailed analysis of these data do not indicate the presence of any statistically significant TeV γ-ray signal from the source direction. Accordingly, we have placed an upper limit of ≤1.18 × 10−12 photons cm−2 s−1 on the integrated γ-ray flux at 3σ significance level.
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| 12. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 13. |
- Rannot, R. C., et al.
(författare)
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TeV gamma-ray Observations of the Blazar Markarian 421 from January to April 2004 with TACTIC Imaging Element
- 2005
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Ingår i: 29th International Cosmic Ray Conference Pune (2005). ; , s. 355-358
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Konferensbidrag (refereegranskat)abstract
- We have observed the blazar Markarian 421 (z=0.031 ) with the TACTIC gamma- ray telescope having thresholdenergy of 1.5TeV at Mt. Abu Rajasthan India from January to April 2004. Observations were made intracking mode for a total of 84(on) /16 (off-source) hours with its imaging element equipped with a 349- pixelPMTs camera. During this period, we nd an evidence of a TeV gamma-ray signal with a statistical signi-cance of 6.8. The differential energy spectrum derived in the energy range 2 - 9 TeV is well represented bya simple power law, with a differential spectral index of 2.800.20.
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| 14. |
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| 15. |
- Oonk, M. H. M., et al.
(författare)
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Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:32
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (<= 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL. (C) 2021 by American Society of Clinical Oncology
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| 16. |
- Van der Kolk, W. L., et al.
(författare)
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Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe
- 2022
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 167:1, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN.Methods. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up.Results. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was di-agnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor >= 30 mm. Bilateral ra-diotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence.Conclusion. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Ibanez, L., et al.
(författare)
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Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2394-2406
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Tidskriftsartikel (refereegranskat)abstract
- During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.
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| 21. |
- Provino, Alessia, et al.
(författare)
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Stability, Crystal Chemistry, and Magnetism of U2+xN21-xB6 and Nb3-yNi20+yB6 and the Role of Uranium in the Formation of the Quaternary U2-zNbzNi21B6 and U delta Nb3-delta Ni20B6 Systems
- 2019
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 58:22, s. 15045-15059
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the U-Ni-B and Nb-Ni-B systems to search for possible new heavy fermion compounds and superconducting materials. The formation, crystal chemistry, and physical properties of U2Ni21B6 and Nb3-yNi20+yB6 [ternary derivatives of the cubic Cr23C6-type (cF116, Fm3m)] have been studied; the formation of the hypothetical U3Ni20B6 and Nb2Ni21B6 has been disproved. U2Ni21B6 [a = 10.6701(2) angstrom] crystallizes in the ordered W2Cr21C6-type, whereas Nb3-yNi20+yB6 [a = 10.5842(1) angstrom] adopts the Mg3Ni20B6-type. Ni in U2Ni21B6 can be substituted by U, leading to the solid solution U2-xNi21+yB6 (0 <= x <= 0.3); oppositely, Nb in Nb3Ni20B6 is partially replaced by Ni, forming the solution Nb3-yNi20+yB6 (0 <= y <= 0.5), none of them reaching the limit corresponding to the hypothetically ordered U3Ni20B6 and Nb2Ni21B6. These results prompted us to investigate quaternary compounds U2-zNbzNi21B6 and U6Nb3-delta Ni20B6: strong competition in the occupancy of the 4a and 8c sites by U, Nb, and Ni atoms has been observed, with the 4a site occupied by U/Ni atoms only and the 8c site filled by U/Nb atoms only. U2Ni21B6, U2.3Ni20.7B6, and Nb3Ni20B6 are Pauli paramagnets. Interestingly, Nb2.5Ni20.5B6 shows ferromagnetism with T-c approximate to 11 K; the Curie-Weiss fit gives an effective magnetic moment of 2.78 mu(B)/Ni, suggesting that all Ni atoms in the formula unit contribute to the total magnetic moment. The M(H) data at 2 K further corroborate the ferromagnetic behavior with a saturation moment of 10 mu(B)/fu (approximate to 0.49 mu(B)/Ni). The magnetic moment of Ni at the 4a site induces a moment in all of the Ni atoms of the whole unit cell (32f and 48h sites), with all atoms ordering ferromagnetically at 11 K. Density functional theory (DFT) shows that the formation of U2Ni21B6 and Nb3Ni20B6 is energetically preferred. The various electronic states generating ferromagnetism on Nb2.5Ni20.5B6 and Pauli paramagnetism on U2Ni21B6 and Nb3Ni20B6 have been identified.
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| 22. |
- Sapru, M. L., et al.
(författare)
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Threshold energy estimate of the proposed MACE gamma-ray telescope at Hanle
- 2005
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Ingår i: 29th International Cosmic Ray Conference Pune (2005). ; , s. 263-266
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Konferensbidrag (refereegranskat)abstract
- The fact that EGRET detected over 250 objects above 100 MeV while only a handful of sources have beendetected above 100 GeV indicates that there is a good chance of detecting a signicant number of these sources(particularly those which do not show a signature of steepening or cut off up to a few GeV), if the thresholdenergy of ground based telescopes is lowered to20 GeV. In the present study, we report the threshold energyestimate of the MACE (Major Atmospheric Cerenkov Experiment) imaging telescope, proposed to be installedin the campus of Indian Astronomical Observatory at Hanle (32.8N, 78.9E, 4200m asl). The results ofthe Monte Carlo simulations carried out with CORSIKA code, suggest that using a pixel threshold of4peand a nearest neighbour quadruplet trigger,-ray energy threshold of15GeV is achievable by the MACEtelescope. Details of the simulation work for estimating the threshold energy along with results obtained arepresented in this paper.
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| 23. |
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| 24. |
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| 25. |
- Annadi, A., et al.
(författare)
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Anisotropic two-dimensional electron gas at the LaAlO3/SrTiO3 (110) interface
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The observation of a high-mobility two-dimensional electron gas between two insulating complex oxides, especially LaAlO3/SrTiO3, has enhanced the potential of oxides for electronics. The occurrence of this conductivity is believed to be driven by polarization discontinuity, leading to an electronic reconstruction. In this scenario, the crystal orientation has an important role and no conductivity would be expected, for example, for the interface between LaAlO3 and (110)-oriented SrTiO3, which should not have a polarization discontinuity. Here we report the observation of unexpected conductivity at the LaAlO3/SrTiO3 interface prepared on (110)-oriented SrTiO3, with a LaAlO3-layer thickness-dependent metal-insulator transition. Density functional theory calculation reveals that electronic reconstruction, and thus conductivity, is still possible at this (110) interface by considering the energetically favourable (110) interface structure, that is, buckled TiO2/LaO, in which the polarization discontinuity is still present. The conductivity was further found to be strongly anisotropic along the different crystallographic directions with potential for anisotropic superconductivity and magnetism, leading to possible new physics and applications.
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| 26. |
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| 29. |
- Dhar, S., et al.
(författare)
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Multi-axial Fatigue of Head-Hardened Pearlitic and Austenitic Manganese Railway Steels: A Comparative Study
- 2020
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Ingår i: Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science. - : Springer Science and Business Media LLC. - 1073-5623. ; 51:11, s. 5639-5652
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Tidskriftsartikel (refereegranskat)abstract
- Switches and crossings (S&Cs) in rail networks suffer from damage and deformation due to severe loading of their complex geometric shapes. This article presents a comparative study of the cyclic deformation characteristics and fatigue behavior of two typical crossing materials, namely head-hardened pearlitic steel and Hadfield manganese steel, as well as the associated microstructural changes. Both uniaxial and biaxial loadings (proportional and non-proportional) are studied. The pearlitic steel endured more cycles to failure for a given strain amplitude compared to the manganese steel. The cyclic response of manganese steel shows significant hardening whereas softening was observed for the pearlitic steel except under biaxial non-proportional loading. The microstructures developed in the two types of steels after deformation are characterized by optical (OM) and transmission electron microscopy (TEM). TEM micrographs reveal that the deformed microstructure of the pearlitic steel consists of threading dislocations and dislocation tangles in the ferrite lamellae. The microstructures in the manganese steel after the different loadings are composed of dislocation cells with dislocation tangles inside, intersected by straight stacking fault lamellae. The observed microstructures are related to the results of the mechanical test, and the suitability of the steels for use in S&Cs is discussed.
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| 34. |
- Heitsch, L., et al.
(författare)
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Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
- 2021
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:1, s. 132-141
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
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| 35. |
- Hoque, S. Manjura, et al.
(författare)
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Detailed study of ultra-soft magnetic properties of Fe74Cu0.8Nb2.7Si15.5B7
- 2011
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Ingår i: Philosophical Magazine. - : Informa UK Limited. - 1478-6435 .- 1478-6443. ; 91:16, s. 2117-2139
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic properties of nanocrystalline Fe74Cu0.8Nb2.7Si15.5B7 alloy, which were rapidly solidified and then annealed at various temperatures between 475 and 650 degrees C for different holding time, have been studied. Grain size, silicon content and the lattice parameter of alpha-Fe(Si) nanograins at the annealing temperatures were determined. Curie temperature of the amorphous phase was determined from the temperature dependence of permeability. For higher annealing temperatures and times, some Si diffused out of the alpha-Fe(Si) phase and formed an ordered DO3 phase of Fe3Si. This changed the overall magnetostriction and average anisotropy of the matrix, which deteriorated the magnetic softness of the material at higher annealing temperatures. Ultra-soft magnetic properties were achieved by averaging the random anisotropy via exchange interaction. Hysteresis loops for samples in as-cast and annealed conditions have also been studied.
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| 36. |
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| 37. |
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| 38. |
- Juliano, Jonathan J, et al.
(författare)
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Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens
- 2016
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 94:1, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens.
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| 39. |
- Kabir, Misha, et al.
(författare)
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DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 17:10, s. 1652-1671
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. Methods Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. Results In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. Conclusions By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.
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| 40. |
- Kamran, Mohammad, et al.
(författare)
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Helicobacter pylori shows asymmetric and polar cell divisome assembly associated with DNA replisome
- 2018
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Ingår i: The FEBS Journal. - : WILEY. - 1742-464X .- 1742-4658. ; 285:13, s. 2531-2547
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Tidskriftsartikel (refereegranskat)abstract
- DNA replication and cell division are two fundamental processes in the life cycle of a cell. The majority of prokaryotic cells undergo division by means of binary fission in coordination with replication of the genome. Both processes, but especially their coordination, are poorly understood in Helicobacter pylori. Here, we studied the cell divisome assembly and the subsequent processes of membrane and peptidoglycan synthesis in the bacterium. To our surprise, we found the cell divisome assembly to be polar, which was well-corroborated by the asymmetric membrane and peptidoglycan synthesis at the poles. The divisome components showed its assembly to be synchronous with that of the replisome and the two remained associated throughout the cell cycle, demonstrating a tight coordination among chromosome replication, segregation and cell division in H. pylori. To our knowledge, this is the first report where both DNA replication and cell division along with their possible association have been demonstrated for this pathogenic bacterium.
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| 41. |
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| 44. |
- Nitharwal, Ram G., et al.
(författare)
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DNA binding activity of Helicobacter pylori DnaB helicase : the role of the N-terminal domain in modulating DNA binding activities
- 2012
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 279:2, s. 234-250
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Tidskriftsartikel (refereegranskat)abstract
- Replicative helicases are major motor proteins essential for chromosomal DNA replication in prokaryotes. Usually hexameric in solution, their DNA binding property must have different roles at stages ranging from the loading onto a branched structure at initiation from the origin to the highly processive translocation during elongation. Here, we have analysed the DNA binding activity of Helicobacter pylori (Hp) replicative helicase, DnaB. The results indicate that while the C-terminal region is important for its DNA binding activity, the N-terminus appears to dampen the proteins affinity for DNA. The masking activity of the N-terminus does not require ATP or hexamerization of HpDnaB and can be overcome by deleting the N-terminus. It can also be neutralized by engaging the N-terminus in an interaction with a partner like the C-terminus of DnaG primase. The inhibitory effect of the N-terminus on DNA binding activity is consistent with the 3D homology model of HpDnaB. Electron microscopy of the HpDnaBssDNA complex showed that HpDnaB preferentially bound at the ends of linear ssDNA and translocated along the DNA in the presence of ATP. These results provide an insight into the stimulatory and inhibitory effects of different regions of HpDnaB on DNA binding activities that may be central to the loading and translocation functions of DnaB helicases.
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| 45. |
- Sharma, Atul, et al.
(författare)
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Helicobacter pylori single-stranded DNA binding protein - functional characterization and modulation of H-pylori DnaB helicase activity
- 2009
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:2, s. 519-531
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, an important bacterial pathogen, causes gastric ulcer and gastric adenocarcinoma in humans. The fundamentals of basic biology such as DNA replication are poorly understood in this pathogen. In the present study, we report the cloning and functional characterization of the single-stranded DNA (ssDNA) binding protein from H. pylori. The N-terminal DNA binding domain shows significant homology with E. coli single-stranded DNA binding protein (SSB), whereas the C-terminal domain shows less homology. The overall DNA-binding activity and tetramerization properties, however, remain unaffected. In in vitro experiments with purified proteins, H. pylori (Hp) SSB bound specifically to ssDNA and modulated the enzymatic ATPase and helicase activity of HpDnaB helicase. HpSSB and HpDnaB proteins were co-localized in sharp, distinct foci in exponentially growing H. pylori cells, whereas both were spread over large areas in its dormant coccoid form, suggesting the absence of active replication forks in the latter. These results confirm the multiple roles of SSB during DNA replication and provide evidence for altered replicative metabolism in the spiral and coccoid forms that may be central to the bacterial physiology and pathogenesis.
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| 46. |
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| 47. |
- Singh, A., et al.
(författare)
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Solar Assisted Gasification
- 2019. - 1
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Ingår i: Advances in Solar Energy Research. - Singapore : Springer. - 9789811333019 - 9789811333026 ; , s. 551-576
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Bokkapitel (refereegranskat)
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| 48. |
- Thakur, H., et al.
(författare)
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Investigation of continuous stirred tank reactors for improving the mixing in anaerobic digestion : A numerical study
- 2023
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Ingår i: Results in Engineering (RINENG). - : Elsevier. - 2590-1230. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, mechanical impeller mixing has been analyzed through CFD which has proven to be a useful method for simulating mixing before manufacturing the digester. In this work, simulations were done for five different digester designs for TS level of 12.1%. While the fifth digester was cylindrical, the other four were cubical in design with varying impeller diameters and the number of impellers. The power law model was used to resemble the sewage sludge as a non-Newtonian fluid. The modified versions of dead volume and uniformity index were used along with velocity gradient and mixing energy level to quantify the quality of mixing. An analysis of the temperature distributions during mixing and heating was done using a thermal study. The operating speed of 250 rpm was finalized after testing at continuously increasing speeds from 50 to 600 rpm for a flat blade type impeller. As per the thermal model, a 250-W heater raised the temperature by around 15 °C in just 10 min. It was found that cylindrical vessels worked better than cubical digesters and larger impellers also helped in improving the mixing. The cylindrical digester which achieved about 67% homogeneity at a mixing energy level of around 0.95 W/m3, was the optimum design among the investigated digesters. © 2023 The Authors
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